OBJECTIVE The exocrine pancreas is increasingly implicated in type 1 diabetes. Noninvasive biomarkers of exocrine function, fecal elastase-1 (FE-1) and serum immunoreactive trypsin (IRT), may provide early insight into disease pathogenesis. We investigated the temporal relationship between exocrine biomarkers and type 1 diabetes development in children. RESEARCH DESIGN AND METHODS FE-1 and IRT concentrations were measured prospectively in 301 at-risk children followed in the Environmental Determinants of Islet Autoimmunity (ENDIA) cohort from birth. A total of 216 children provided 1,679 stool samples; 242 provided 1,014 serum samples. Biomarker trajectories were compared between children who developed islet autoimmunity or type 1 diabetes and age- and sex-matched control children negative for autoantibodies in a nested case-control design. Adjusted linear mixed models were used. RESULTS Two biomarker patterns were observed. FE-1 concentrations were lower during the first 6 months of life in children who subsequently developed multiple islet autoantibodies or type 1 diabetes (β-coefficient at birth −0.61 [95% CI −1.04, −0.17]; P = 0.006; β-coefficient at 3 months −0.39 [95% CI −0.69, −0.09]; P = 0.010); IRT concentrations were lower in children who developed type 1 diabetes 12 months (β = −0.30 [95% CI −0.58, −0.02]; P = 0.034) and 18 months (β = −0.40 [95% CI −0.71, −0.10]; P = 0.008) before type 1 diabetes diagnosis. CONCLUSIONS Changes in exocrine biomarkers were detectable early in the natural history of type 1 diabetes, with a delayed rise of FE-1 in infants who later progressed to multiple islet autoantibodies or type 1 diabetes and a decrease in IRT following islet autoantibody seroconversion.
OBJECTIVE To examine associations between diabetes status and self-reported discrimination based on race among U.S. adults with and without diabetes. RESEARCH DESIGN AND METHODS We analyzed 2022–2023 Behavioral Risk Factor Surveillance System data from 328,056 adults completing the Reactions to Race module and reporting diabetes status. Experiences of racial discrimination at work, in health care, or elsewhere, and related physical symptoms, were categorized as any versus none. Weighted prevalence and multivariable logistic regression were stratified by diabetes status. RESULTS Discrimination based on race was reported by 14.2% of adults with diabetes and 12.5% without diabetes. Patterns were similar across age, metropolitan status, and employment subgroups. In both groups, discrimination was associated with race and ethnicity, age, sex, employment, poor mental health, and current smoking. CONCLUSIONS Experiences of racial discrimination were common among U.S. adults and were reported more frequently by adults with diabetes. Because discrimination can contribute to chronic stress, reduced access to high-quality care, and barriers to diabetes self-management, consideration of racism-related exposures is important in efforts to understand and address diabetes disparities.
Objective: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have demonstrated cardiorenal benefits in individuals with type 2 diabetes, but safety data in older adults remain limited. We evaluated the real-world safety of SGLT2is compared with dipeptidyl peptidase-4 inhibitors (DPP4is) among individuals aged ≥ 75 years with type 2 diabetes. Research Design and Methods: We conducted a population-based, active-comparator, new-user cohort study using administrative health databases from British Columbia, Canada. We included individuals aged ≥ 75 years with type 2 diabetes initiating SGLT2is or DPP4is between January 1, 2021, and December 31, 2023. Primary outcomes were infection, diabetic ketoacidosis, acute kidney injury, falls, fracture, and all-cause hospitalization. Cox regression with propensity score-based standardized mortality ratio weighting was used to estimate hazard ratios. Results: The study included 4,997 SGLT2i initiators (median age, 79 years; 37% female) and 1,289 DPP4i initiators (median age, 82 years; 50% female). Compared with DPP4i initiation, SGLT2i initiation was associated with lower risks of acute kidney injury (hazard ratio [HR]: 0.76, 95% CI: 0.60 to 0.95) and all-cause hospitalization (HR: 0.87, 95% CI: 0.77 to 0.98), with no difference in risk of infection. No differences were observed in risk of diabetic ketoacidosis, falls, or fractures, although confidence intervals were compatible with both benefit and harm. Conclusions: In individuals aged ≥ 75 years with type 2 diabetes, SGLT2i initiation was not associated with increased risk of harm compared with DPP4i initiation, although estimates were imprecise for some outcomes. These findings may support consideration of SGLT2is as a treatment option in this population.
Objective: To evaluate the comparative effectiveness of semaglutide versus dulaglutide or liraglutide in patients with diabetes receiving maintenance hemodialysis. Research Design and Methods: Using 2011-2022 US Renal Data System and Medicare data, we emulated a target trial evaluating semaglutide versus dulaglutide or liraglutide in patients receiving hemodialysis. Overlap weights were used to adjust for confounders. Fine-Gray models were used to assess death on dialysis and hospitalization. A generalized estimating equation was used for repeated measures of body weight. Results: We identified 1,312 semaglutide and 2,601 dulaglutide or liraglutide users. After overlap weighting, the effective sample size was 3,200 patients (mean age 61; 63% White; 28% Black; 52% male; median BMI 34 [29 – 40] kg/m2; median follow-up 1.1 [0.6 – 1.9] years). Semaglutide versus dulaglutide or liraglutide was associated with a mortality on dialysis subdistribution hazard ratio (sHR) of 0.82 (95% CI, 0.70 to 0.97; 1-year cumulative incidence 11% versus 13%) and all-cause hospitalization sHR of 0.91 (95% CI, 0.83 to 0.99; 1-year incidence 57% versus 62%). Body weight loss was higher with semaglutide (-4.8% [95% CI, -5.3% to -4.2%]) at 1-year (versus -3.4% [95% CI, -3.9% to -3.1%]). Direct comparisons of semaglutide versus dulaglutide showed similar results (mortality: sHR 0.82 [0.69 to 0.97]; hospitalization: sHR 0.88 [0.81 to 0.97]), but semaglutide versus liraglutide showed no statistically significant benefit for mortality or hospitalization. Conclusions: Among patients with diabetes receiving hemodialysis and equipoise between semaglutide and dulaglutide or liraglutide, semaglutide may be the preferred GLP-1 compared to dulaglutide.
